So-called depot or slow-release pharmaceutical forms with controlled release are becoming increasingly important in pharmaceutical therapy as a result of an improved, longer-lasting therapeutic effect and the fact that the dosage form needs to be administered less frequently. Besides the coated slow-release forms where the release is controlled by a coating, the usage of matrix forms in which the active ingredient is present embedded in a base from which it slowly diffuses out on contact with gastric or intestinal juice is becoming more frequent. These forms can be produced by various technologies such as, for example, direct tableting or wet granulation. The matrix formers frequently employed are erodable substances or gel formers such as hydroxypropylmethylcellulose or xanthan, which control the release on contact with aqueous media.
Disadvantages of these products and processes is that the release depends greatly on the mode of granulation, the particle size of the starting materials and granule particles, the compressive force and on the salt content or on the osmolarity of the release medium. There are often variations in release from tablet to tablet and from batch to batch. In addition, such tablets frequently exhibit insufficient mechanical stability, meaning a low resistance to crushing and a high friability.
EP-A 1166776 describes a process for producing oral dosage forms with a release-slowing effect, in which a preformulated mixture of polyvinyl acetate and polyvinylpyrrolidone is granulated with active ingredients by heating to 40-130° C. The granulation is brought about by softening the polyvinyl acetate to give a tacky material, and thus the powder particles cohere to give granule particles. The results achieved therewith in terms of the release of the active ingredient and the mechanical stability of the dosage form were reasonably good. Nevertheless, the granules obtained in this way exhibit certain disadvantages, for example in terms of the granule size and the porosity of the granule particles formed, which influence the release. The process becomes more difficult to control thereby.
EP-A 1138321 likewise describes tablets from a preformulated mixture of polyvinyl acetate and polyvinylpyrrolidone which are produced by direct tableting of physical powder mixtures or conventional granulation techniques and which likewise exhibit the disadvantages mentioned.